A collaboration of researchers from Johns Hopkins University School of Medicine, the National Institutes of Health, and Florida State University are working to discover existing drugs that may work against Zika infections.

So far, they have screened 6,000 compounds that are either already approved for use in humans or are currently in late-stage clinical trials, and have found two classes of compounds that may be effective.

"It takes years if not decades to develop a new drug," says Hongjun Song, Ph.D. of Johns Hopkins. "In this sort of global health emergency, we don't have that kind of time."

"So instead of using new drugs, we chose to screen existing drugs," adds Johns Hopkins professor of neurology Guo-li Ming. "In this way, we hope to create a therapy much more quickly."

The new findings are an extension of previous work by the research team, which found that Zika mainly targets specialized stem cells that give rise to neurons in the brain's outer layer, the cortex.

The researchers observed Zika's effects in two- and three-dimensional cell cultures called "mini-brains," which share structures with the human brain and allow researchers to study the effects of Zika in a more accurate model for human infection.

In the current study, the research team exposed cell cultures to the Zika virus and the drugs one at a time, measuring for indicators of cell death.

Typically, after Zika infection, the damage done to neural cells is "dramatic and irreversible," says Hengli Tang of Florida State University. However, some of the compounds tested allowed the cells to survive longer and, in some cases, fully recover from infections.

When the surviving cells were closely examined, Ming said the promising drugs could be divided into two classes: neuroprotective drugs, which prevent the activation of mechanisms that cause cell death, and antiviral drugs, which slow or stop viral infection or replication.

Song said that three drugs showed results positive enough to warrant further study: PHA-690509, an investigational compound with antiviral properties; emricasan, now in clinical trials to reduce liver damage from hepatitis C virus and shown to have neuroprotective effects; and niclosamide, a drug already used in humans and livestock to combat parasitic infections, which worked as an antiviral agent in the Zika experiments.

Song said that the three drugs "are very effective against Zika in the dish, but we don't know if they can work in humans in the same way." For example, he says, although niclosamide can safely treat parasites in the human gastrointestinal tract, scientists have not yet determined if the drug can even penetrate the central nervous system of adults or a fetus inside a carrier's womb to treat the brain cells targeted by Zika.

The researchers say their next steps include testing the efficacy of these drugs in animal models to see if they have the ability to combat Zika in vivo.

Although Zika was first identified in 1947, it gained international attention when it was shown that the virus caused an increase in microcephaly, a severe birth defect that causes underdeveloped brains.

The virus is now spreading in the Miami area of Florida, and in an effort to contain the virus, the FDA has urged that blood donations nationwide be tested for the virus.

The Zika virus is normally transmitted from mosquito bites or from an infected person through sexual contact. Recent news reports have shown the virus to be hardy. Zika may persist in newborns for months, and may continue to replicate in the vagina for several days after infection. A recent case found that the virus was spread through sex by a man who had no symptoms of the disease.

A new report found that female mosquitoes can transmit the virus to their offspring, making the spread of the disease harder to control, and emphasizing the need for programs that kill both mosquitoes and their eggs.

If you live in an area threatened by Zika, you can help stop its spread by removing any containers on your property that can collect and hold standing water.

A collaboration of researchers from Johns Hopkins University School of Medicine, the National Institutes of Health, and Florida State University are working to discover existing drugs that may work against Zika infections.
So far, they have screened 6,000 compounds that...

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